Abstract
Periodontal disease is a chronic infection of periodontal tissue characterized by extracellular matrix (ECM) degradation due to increased expression of plasminogen activators and matrix metalloproteinases (MMPs) and various proinflammatory cytokines, including interleukin (IL)-17. Successful regeneration of damaged periodontal tissues depends on the proper functionality of periodontal ligament mesenchymal stem cells (PDLMSCs), especially the production of extracellular matrix proteases. We investigated the influence of IL-17 on ECM remodeling through modulation of urokinasetype plasminogen activator (uPA) and MMP2/MMP9 expression in human PDLMSCs at mRNA, protein and activity levels using by RT-PCR, Western blotting and zymography, respectively. Investigation of the involvement of MAPKs in these processes in PDLMSCs was determined by Western blotting, as well as by utilizing specific p38 and MEK1/2 inhibitors. Our results show that IL-17 activates MAPK signaling in PDLMSCs. Moreover, IL-17 had no effect on MMP9 expression, but it stimulated uPA and MMP2 gene and protein expression in PDLMSCs through the activation of the ERK1/2 MAPK signaling pathway. The obtained data suggest that IL-17 contributes to ECM degradation in the periodontal ligament by stimulating uPA and MMP2 expression and activity in PDLMSCs. This information is important for understanding periodontal disease development and defining future directions of its treatment.
Highlights
Periodontal disease is a progressive and degenerative disease of the periodontium, teethsupporting tissue that is composed of the gingiva, periodontal ligament (PDL), tooth cementum and alveolar bone, which leads to the loss of connective tissue and bone support and teeth loss [1]
periodontal ligament mesenchymal stem cells (PDLMSCs) showed the potential to differentiate into cells of osteogenic, chondrogenic and adipogenic lineage since a high level of alkaline phosphatase (ALP) activity, calcium and proteoglycan deposition and lipid droplets were observed in PDLMSCs cultured in specific differentiation media compared with cells cultured in regular growth medium (GM) (Fig. 1B)
IL-17 stimulates urokinase-type plasminogen activator (uPA) and MMP2 expression in PDLMSCs Since uPA and MMP2/MMP9 have been shown to be implicated in periodontal tissue degradation [5,8], first we aimed to determine whether IL-17 modulates the expression of these proteolytic enzymes
Summary
Periodontal disease is a progressive and degenerative disease of the periodontium, teethsupporting tissue that is composed of the gingiva (gums), periodontal ligament (PDL), tooth cementum and alveolar bone, which leads to the loss of connective tissue and bone support and teeth loss [1]. It was determined that deficiency in plasminogen activators leads to the elongation of mouse bones and increased bone mass, which points to the importance of the plasminogen system in bone matrix degradation [7]. In a recent study it was proposed that uPA contributes to periodontal tissue degradation directly and indirectly through the activation of latent forms of MMPs [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
